On September 1, 2014 Exelixis reported top-line results from the final analysis of COMET-1 (NCT01605227), the phase 3 pivotal trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide (Press release Exelixis, SEP 1, 2014, View Source [SID:1234500718]). The trial did not meet its primary endpoint of demonstrating a statistically significant increase in overall survival (OS) for patients treated with cabozantinib as compared to prednisone. The median OS for the cabozantinib arm of the trial was 11.0 months versus 9.8 months for the prednisone arm (hazard ratio 0.90; 95% confidence interval 0.76 – 1.06; p value 0.212).

The COMET-1 results are the subject of ongoing analyses. Exelixis will submit additional data, including secondary and exploratory endpoints, for presentation at a future medical conference. Besides OS, the exploratory endpoint of progression-free survival (PFS) as assessed by the investigators is the only time-to-event-based endpoint for which data are available. Median PFS was 5.5 months for the cabozantinib arm of the trial versus 2.8 months for the prednisone arm (hazard ratio 0.50; 95% confidence interval 0.42 – 0.60; p value <0.0001). Safety data were consistent with those observed in earlier-stage trials of cabozantinib in mCRPC. As a result of the outcome of COMET-1, Exelixis will initiate a significant workforce reduction to enable the company to focus its financial resources on the late-stage clinical trials of cabozantinib in metastatic renal cell carcinoma (the METEOR trial) and advanced hepatocellular carcinoma (the CELESTIAL trial). The company will reduce its workforce by approximately 70 percent, or approximately 160 employees, resulting in approximately 70 remaining employees. Exelixis anticipates the one-time restructuring charge associated with the workforce reduction to be approximately $6 million - $8 million, with the majority to be completed by the end of the fourth quarter of 2014. As a result of this and other cost-saving measures contemplated, the company anticipates that it has sufficient cash to support its operations through the release of top-line results of the METEOR trial next year. More financial details will be provided by the company in its third quarter 2014 financial report. "We are very disappointed that COMET-1 did not meet its primary endpoint of extending overall survival in men with mCRPC," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We are grateful to the patients, physicians, nurses, caregivers, and other study team members who participated in the trial. We remain focused on the development program for cabozantinib beyond mCRPC, including the ongoing METEOR and CELESTIAL phase 3 pivotal trials, from which we expect top-line data in 2015 and 2017, respectively." Dr. Morrissey continued, "We have thoughtfully prepared for this scenario and the resulting very difficult decisions. The workforce reduction we have announced today is necessary to significantly reduce our corporate operating expenses. I would like to personally express my deep appreciation to the talented and dedicated Exelixis employees who will be impacted by these actions, both for their commitment to Exelixis and for their tremendous contributions to patients with cancer." Based on the outcome of COMET-1, Exelixis has deprioritized the clinical development of cabozantinib in mCRPC. Enrollment in COMET-2, which is the second pivotal trial in mCRPC and evaluates pain palliation, has been halted. The company expects top-line data before the end of this year. Based on the outcome of COMET-2, Exelixis will discuss with regulatory authorities the potential regulatory path, if any, of cabozantinib in mCRPC. Other company-sponsored studies in mCRPC, including a randomized phase 2 study of cabozantinib in combination with abiraterone, will also be halted.